Did Sarepta Expose the Flaw in FDA Review Process? 
[Thursday, August 22, 2019]

FDA’s decisions about the products it reviews can be mind-bogglingly subjective. When two products, for the same indication, with almost identical clinical development plans, and developed by the same company, have extremely contrasting FDA review outcomes it makes it impossible for the public to know the true reasons for such diverse decisions. Three year ago, in 2016, a small Massachusetts company, Sarepta was successful in winning FDA approval for its drug to treat a rare disease, Exondys 51, against mostly negative opinions from FDA’s internal reviewers and Advisory Committee. Sarepta was the master of spin and used public sympathy very effectively to force FDA’s hand. The pundits wrote millions of words trying to decipher the reason for FDA’s generosity for Sarepta. The general consensus was that FDA wanted to help patients with a rare disease and no treatment, to get some hope. This week, in a literal about-turn the same company using a very similar clinical development strategy failed to get approval for another drug, Vyondys 53, for the same disease for seemingly minor issues. The new drug is for an even smaller group of patients with Duchenne Muscular Dystrophy (DMD) and is an improvement on the previous drug. It used the same surrogate endpoints as the previous approval and has almost identical study design. Although the complete response letter (CRL) was not made public by Sarepta, it announced that the main reasons for the rejection were risk of infection at infusion ports and renal toxicity observed in animal studies at 10 times the human dose. Both these reasons, if true, seem very flimsy. The risk of infection at infusion ports is widely known for all infused drugs and can be easily controlled. And the issue of toxicity at higher than human doses can be addressed by adding risk mitigation measures since this is a drug administered only under a physician’s supervision. Some pundits have argued that FDA’s negative decision this time is perhaps based on the bad blood between FDA’s reviewers and the company from the last approval decision, since it is the same set of reviewers whose negative options were ignored in 2016 by the FDA brass. Others have argued that Sarepta is no longer a small company; it is worth $8 billion with a $300-400 million per year revenue from Exondys 51, making FDA less sympathetic to its lack of data. Still others believe that since DMD now has a drug for its treatment, and FDA has already given “hope” to the patients earlier, FDA does not feel the need to approve another drug for this rare disease. All of these so-called “reasons” try to highlight only one common theme; that FDA is highly subjective in its decision-making process about drugs it reviews. The law should not discriminate between big and small companies, new and old drugs, or used for subjective application of standards. So, if any of the above is true, it would be black eye for the Agency that proudly calls itself a “science-based” organization. But FDA is not talking and Sarepta has so far refused to release the CRL. With Sarepta’s history of spinning information, it is hard to know if the FDA’s process is flawed or Sarepta is at its old game. Your guess is as good as mine.